The aim of this project is to use drugs and other biologically active agents such as hormones to explore the mechanism and prevent the expression of reactions involving immediate hypersensitivity and cellular immunity. Experimentation will primarily involve two developed and pertinent in vitro models: antigen induced, IgE-mediated histamine release from human leukocytes (basophils) and target cell (mastocytoma) destruction (Cr5I release) by sensitized allogeneic mouse splenic lymphocytes. Appropriate in vivo situations (e.g. primate skin testing; graft rejection) will be investigated whenever warranted to verify the in vitro work. Moreover, some experimentation in clinical settings (funded by our Allergy Center or Lung Center) will be carried out as it becomes desirable. We will first focus our attention on drugs which affect the cyclic AMP system (i.e., adenylcyclase stimulators, such as the catecholamines and prostaglandins; phosphodiesterase inhibitors, such as the methylxanthine; and cyclic AMP analogs) and the microtubule system (i.e., colchicine, vinblastine, D2O) and will move on to drugs whose mechanism of action is less defined. This work is built on previous experimentation which suggests that the cyclic AMP system and the microtubule system play a role in the mechanism of allergic and cellular immune responses. Our eventual goal is the development of drugs useful in preventing or controlling the clinical expression of disease processes with a pathogenesis involving immediate or delayed hypersensitivity. BIBLIOGRAPHIC REFERENCES: Lichtenstein, L. M. Hormone receptor interaction in the control of allergic and inflammatory reactions. IN: Symposium Proceedings VIII Miles International Symposium, 1976. Lichtenstein, L.M. and Gillespie, E. The effects of the H1 and H2 antihistamines on "allergic" histamine release and its inhibition by histamine. J. Pharm. Exp. Therap. 192: 441-450, 1975.